ST8SIA1 inhibition sensitizes triple negative breast cancer to chemotherapy via suppressing Wnt/ß-catenin and FAK/Akt/mTOR.
Clin Transl Oncol
; 23(4): 902-910, 2021 Apr.
Article
em En
| MEDLINE
| ID: mdl-32939659
BACKGROUND: Chemoresistance is the major cause of therapeutic failure in triple negative breast cancer (TNBC). In this work, we investigated the molecular mechanism for the development of TNBC chemoresistance. METHODS: mRNA and protein levels of ST8SIA1 were analyzed in chemosensitive and chemoresistant TNBC cells and tissues. Proliferation and survival assays were performed to determine the role of ST8SIA1 in TNBC chemoresistance. RESULTS: We found that ST8SIA1 mRNA and protein levels were increased in multiple TNBC cell lines after prolonged exposure to chemotherapeutic drugs. Consistently, retrospective study demonstrated that the majority of TNBC patients who developed chemoresistance displayed upregulation of ST8SIA1. We further found that chemoresistant TNBC cells were more sensitive than chemosensitive cells to ST8SIA1 inhibition in decreasing growth and viability. Consistently, ST8SIA1 inhibition augmented the efficacy of chemotherapy in TNBC cells. Mechanism studies demonstrated that ST8SIA1 inhibition led to suppression of FAK/Akt/mTOR and Wnt/ß-catenin signalling pathways. CONCLUSIONS: These findings provide an explanation for the heterogeneity of chemotherapy responses across TNBC individuals and reveal the supportive roles of ST8SIA1in TNBC chemoresistance.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sialiltransferases
/
Proteínas Proto-Oncogênicas c-akt
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Serina-Treonina Quinases TOR
/
Via de Sinalização Wnt
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Neoplasias de Mama Triplo Negativas
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Female
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Humans
Idioma:
En
Revista:
Clin Transl Oncol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Itália